Affinage

ATXN2

Ataxin-2 · UniProt Q99700

Length
1313 aa
Mass
140.3 kDa
Annotated
2026-06-09
100 papers in source corpus 20 papers cited in narrative 20 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ATXN2 is a cytoplasmic RNA-binding protein that functions in post-transcriptional control by assembling with polyribosomes and poly(A)-binding protein (PABP) to regulate the translation and stability of selected mRNAs (PMID:16835262). It engages polyribosomes through two independent conserved elements — an N-terminal Lsm/LsmAD domain that contacts mRNA directly and a PAM2 motif that binds PABP and promotes polyribosome assembly (PMID:16835262). Through this machinery ATXN2 acts as a selective translational regulator: it binds and controls specific transcripts including RGS8 (PMID:25902068), the N-acetylaspartate-synthesis enzyme transcript Nat8l (PMID:31376479), and m6A-modified TNFRSF1A (TNFR1), the last driving NF-κB and MAPK activation in esophageal carcinoma cells (PMID:34995801). In model organisms it operates within RNA-regulatory complexes — with PAB-1 in the C. elegans germline (PMID:15342467) and with TWENTY-FOUR (TYF) to activate PER translation in Drosophila circadian neurons by promoting TYF–PABP interaction (PMID:23687048). Beyond translation, ATXN2 has broader roles in cell physiology: it regulates centrosome size, microtubule dynamics and cytokinesis in C. elegans via complexes with SZY-20 and modulation of PAR-5 and γ-Tubulin (PMID:27689799, PMID:27559134), acts as an mTOR repressor downstream of AMPK (PMID:27457958), and modifies metabolic and mitochondrial-quality-control programs, including parallel stress-induced regulation with PINK1 (PMID:27597528) and lipid metabolism (PMID:16293225). ATXN2 expression is autoregulated and transcription-factor controlled, serving as a ZBRK1 co-activator on its own promoter (PMID:20926453) and requiring ETS1 for expression (PMID:22914732). CAG-repeat (polyglutamine) expansion in ATXN2 causes spinocerebellar ataxia type 2, in which cytoplasmic mutant protein progressively sequesters PABPC1, TDP-43 and TIA1 into insolubility, suppresses cholesterol biosynthesis, and indirectly perturbs calcium homeostasis in neurons (PMID:22956915, PMID:10973246, PMID:33577922, PMID:26868665).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2000 Medium

    Establishing where mutant ataxin-2 acts addressed whether polyQ pathology required nuclear inclusions, as for other polyQ diseases; it showed SCA2 pathology is cytoplasmic.

    Evidence Immunohistochemistry of human SCA2 brain and transgenic ataxin-2[Q58] mice with neuropathological analysis

    PMID:10973246

    Open questions at the time
    • Does not define the molecular target whose disruption kills Purkinje cells
    • Mechanism linking cytoplasmic microaggregates to dendritic loss unresolved
  2. 2004 High

    The first physiological role was defined by showing the ortholog complexes with PABP to control germline translation, framing ATXN2 as a translational regulator rather than a structural protein.

    Evidence Co-IP and genetic loss-of-function with germline phenotyping in C. elegans

    PMID:15342467

    Open questions at the time
    • Direct mRNA targets not identified
    • Whether the human ortholog uses the same KH-protein circuitry untested
  3. 2006 High

    The molecular basis of ATXN2's translational function was mapped, showing two separable domains tether it to polyribosomes and PABP — defining how it accesses mRNA.

    Evidence Polyribosome sedimentation, Co-IP, and domain mutagenesis in Drosophila and human cells

    PMID:16835262

    Open questions at the time
    • Sequence specificity of Lsm/LsmAD mRNA binding undefined
    • Does not show whether binding activates or represses translation
  4. 2010 Medium

    Discovery of ZBRK1 partnership revealed a feedback loop in which ATXN2 co-activates its own transcription, addressing how ATXN2 levels are set.

    Evidence Co-IP, ChIP, luciferase promoter assays with knockdown/overexpression in cell culture

    PMID:20926453

    Open questions at the time
    • Physiological relevance of autoregulation in neurons untested
    • Single lab, no in vivo confirmation
  5. 2012 Medium

    Identifying ETS1 as a required transcriptional activator extended ATXN2 expression control and resolved which start codon is functional.

    Evidence EMSA, ChIP-PCR, promoter luciferase deletions, transgenic mice, shRNA

    PMID:22914732

    Open questions at the time
    • Tissue/context dependence of ETS1 regulation unclear
    • Upstream signals controlling ETS1 at the ATXN2 promoter unknown
  6. 2012 Medium

    Linking expansion to PABPC1 loss and FBXW8 induction connected polyQ ATXN2 to disrupted RNA-binding partner availability and to a candidate clearance route.

    Evidence CAG42 knock-in mouse, soluble/insoluble fractionation, in vitro FBXW8 degradation assay

    PMID:22956915

    Open questions at the time
    • Whether PABPC1 sequestration is the proximal cause of toxicity untested
    • FBXW8's role only partial in vitro
  7. 2015 High

    RNA-IP identification of RGS8 as a selective target provided direct evidence that ATXN2 controls specific mRNA translation and that expansion impairs this function.

    Evidence RNA-IP, deep RNA-seq, in vitro coupled translation, BAC transgenic mice

    PMID:25902068

    Open questions at the time
    • Recognition determinants on RGS8 mRNA not mapped
    • Whether RGS8 loss drives the neuronal phenotype not established
  8. 2015 Medium

    Reciprocal Co-IP placed ATXN2 in a complex with FBXW8 and PARK2 and showed expansion co-sequesters these partners, extending the aggregation pathology to ubiquitin-pathway components.

    Evidence In vitro and in vivo Co-IP, fractionation immunoblot, qPCR in patient fibroblasts/blood

    PMID:25790475

    Open questions at the time
    • Whether FBXW8-mediated degradation is functionally protective in vivo untested
    • Stoichiometry of co-sequestration unknown
  9. 2015 Medium

    Testing repeat-associated non-AUG translation clarified that RAN products are a minor, length-independent contributor relative to canonical ATXN2 translation.

    Evidence Luciferase reporters lacking the AUG, anti-polyQ Western, promoter/truncation variants in cells

    PMID:26086378

    Open questions at the time
    • In vitro reporter only; endogenous RAN product abundance in patient tissue not measured
    • Pathological contribution untested
  10. 2016 Medium

    C. elegans studies defined a cell-division role, showing ATX-2 complexes with SZY-20 and controls centrosome size, microtubule dynamics, and ZEN-4 midzone targeting via PAR-5.

    Evidence RNA-independent Co-IP, RNAi, live imaging, genetic epistasis in C. elegans embryos

    PMID:27559134 PMID:27689799

    Open questions at the time
    • Whether mammalian ATXN2 performs an analogous mitotic function untested
    • Molecular link between RNA-regulatory and centrosomal roles unclear
  11. 2016 Medium

    Genetic placement of ATX-2 as an mTOR repressor downstream of AMPK connected ATXN2 to nutrient-sensing and cell-size/fat control.

    Evidence RNAi, overexpression, pathway epistasis, direct interaction assay with Rab-GDIβ in C. elegans

    PMID:27457958

    Open questions at the time
    • RHEB-shuttling mechanism inferred, not directly demonstrated
    • Conservation in mammals not shown
  12. 2017 Medium

    Loss-of-function transcriptomics revealed ATXN2 as a modifier of PINK1 and calcium-homeostasis genes, broadening its role to mitochondrial quality control and stress signaling.

    Evidence KO mouse RNA-seq/qPCR/immunoblot, SH-SY5Y siRNA and starvation stress; two mouse models with negative ITPR1 Co-IP

    PMID:26868665 PMID:27597528

    Open questions at the time
    • Whether PINK1 regulation is transcriptional or translational unresolved
    • Calcium-gene effects shown to be indirect; intermediary unknown
  13. 2019 Medium

    Pre-symptomatic Nat8l downregulation in CAG100 knock-in mice linked ATXN2 dysfunction to an early, in-vivo-measurable metabolic deficit.

    Evidence CAG100 knock-in mouse, RT-qPCR, in vivo MR spectroscopy, transcriptome profiling

    PMID:31376479

    Open questions at the time
    • Direct binding of ATXN2 to Nat8l mRNA not demonstrated here
    • Causal contribution of NAA loss to disease untested
  14. 2021 Medium

    Spinal-cord analysis showed mutant ATXN2 aggregates sequester TDP-43 and TIA1 and suppress cholesterol biosynthesis, tying SCA2 to ALS-related RNA pathology and lipid metabolism.

    Evidence CAG100 knock-in mouse, triple immunofluorescence, immunoblot, RT-qPCR, gas chromatography

    PMID:33577922

    Open questions at the time
    • Order of events between sequestration and cholesterol loss unresolved
    • Whether cholesterol restoration is protective untested
  15. 2022 Medium

    Identification of m6A-modified TNFRSF1A as a target connected ATXN2 translational activation to inflammatory NF-κB/MAPK signaling in cancer cells.

    Evidence m6A-seq, RNA-IP, overexpression/knockdown, pathway immunoblots in ESCC cells

    PMID:34995801

    Open questions at the time
    • Whether m6A recognition is direct or via a reader untested
    • Relevance to neuronal ATXN2 function unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how ATXN2's sequence-specific mRNA selection works mechanistically and how its diverse cellular roles (translation, centrosome/cytokinesis, mTOR, mitochondrial QC) are coordinated by a single protein.
  • No structural model of target-mRNA recognition by the Lsm/LsmAD domain
  • Unifying biochemical logic across translational and non-translational roles undefined
  • Proximal toxic species in polyQ expansion not pinpointed

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 4 GO:0045182 translation regulator activity 4 GO:0140110 transcription regulator activity 1
Localization
GO:0005829 cytosol 2 GO:0005815 microtubule organizing center 1 GO:0005840 ribosome 1
Pathway
R-HSA-8953854 Metabolism of RNA 4 R-HSA-1640170 Cell Cycle 2 R-HSA-9609507 Protein localization 1
Partners
FBXW8PABPC1PARK2SZY-20TDP-43TIA1TYFZBRK1
Complex memberships
ATXN2-PABP polyribosome complex

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 Ataxin-2 and its Drosophila homolog ATX2 physically assemble with polyribosomes and poly(A)-binding protein (PABP). Assembly with polyribosomes is mediated independently by two distinct conserved regions: an N-terminal Lsm/LsmAD domain and a PAM2 motif. The PAM2 motif mediates physical interaction with PABP and also promotes polyribosome assembly, suggesting ATX2 binds mRNA directly through its Lsm/LsmAD domain and indirectly via PABP. Co-immunoprecipitation, polyribosome sedimentation assays, domain deletion/mutation analysis in Drosophila and human cells Human molecular genetics High 16835262
2004 C. elegans ATX-2 (ortholog of human ataxin-2) forms a complex with PAB-1 (cytoplasmic poly(A)-binding protein) and is required for germline development. Loss of ATX-2 causes reduced germline stem cell proliferation and abnormal masculinization, resulting from inappropriate translational regulation normally mediated by GLD-1 and MEX-3 KH-domain proteins. Co-immunoprecipitation, genetic loss-of-function (RNAi/mutant), phenotypic analysis in C. elegans germline Development (Cambridge, England) High 15342467
2002 Drosophila Datx2 (ataxin-2 homolog) is a dosage-sensitive regulator of actin filament formation. Loss-of-function or overexpression results in actin filament formation defects, female sterility, and tissue degeneration. Datx2 does not assemble with actin filaments, indicating its role in actin regulation is indirect. Genetic loss-of-function and overexpression transgenic analysis, immunostaining of actin filaments in Drosophila Genetics Medium 12524342
2013 Drosophila ATX2 is required for circadian locomotor behavior and PER accumulation in circadian pacemaker neurons. ATX2 functions as an activator of PER translation by forming a complex with TWENTY-FOUR (TYF) and promoting TYF's interaction with poly(A)-binding protein (PABP). Genetic loss-of-function, co-immunoprecipitation, behavioral assays, immunostaining in Drosophila Science (New York, N.Y.) High 23687048
2005 Ataxin-2 knockout mice are viable but show adult-onset obesity on a fat-enriched diet, and female Sca2-/- mice show reduced birth frequency (segregation distortion). No major histological abnormalities were observed in surviving knockout mice, indicating ataxin-2 is not essential for development but affects metabolic regulation. Gene knockout (homologous recombination), genotypic analysis, weight measurement, histological analysis in mice Biochemical and biophysical research communications Medium 16293225
2012 Expanded ATXN2 (CAG42 knock-in) sequesters PABPC1 into insolubility in mouse cerebellum. In vitro, ATXN2 overexpression reduces PABPC1 levels. FBXW8 is selectively induced in old CAG42 knock-in cerebellum and decreases the level of expanded insoluble ATXN2 protein in vitro, suggesting FBXW8 partially alleviates ATXN2 aggregation. Knock-in mouse model, immunoblot (soluble/insoluble fractionation), cell culture ATXN2 overexpression, transcriptome profiling, in vitro FBXW8 degradation assay PLoS genetics Medium 22956915
2015 ATXN2 interacts selectively with RGS8 mRNA as shown by RNA immunoprecipitation. Expanded polyglutamine ATXN2 impairs this interaction, reduces RGS8 mRNA levels, and reduces RGS8 protein levels more severely than mRNA levels. Mutant ATXN2 reduces RGS8 expression in an in vitro coupled translation assay, supporting a role for ATXN2 in translational regulation of RGS8. RNA immunoprecipitation, transcriptome analysis by deep RNA-sequencing, in vitro coupled translation assay, BAC transgenic mouse model PLoS genetics High 25902068
2010 ZBRK1 (a KRAB zinc-finger transcriptional regulator) is an interaction partner of ataxin-2, and elevated ZBRK1 levels increase ataxin-2 levels. A ZBRK1/ataxin-2 complex regulates SCA2 gene transcription via ZBRK1-binding sites in the SCA2 promoter. Ataxin-2 thus acts as a co-activator of ZBRK1 to upregulate its own transcription. Co-immunoprecipitation, chromatin immunoprecipitation, luciferase promoter assay, siRNA knockdown, overexpression in cell culture Human molecular genetics Medium 20926453
2012 ETS1 transcription factor binds the ATXN2 promoter at an ETS-binding site and is required for ATXN2 expression. ETS1 overexpression increases endogenous ATXN2 expression; dominant-negative ETS1 or ETS1 shRNA reduces ATXN2-luciferase expression. The second of two possible start codons is confirmed as the functional start codon in ATXN2. Electromobility supershift assay, chromatin immunoprecipitation PCR, luciferase promoter deletion analysis, transgenic mice, shRNA knockdown Human molecular genetics Medium 22914732
2016 C. elegans ATX-2 (ataxin-2 ortholog) regulates centrosome size and microtubule dynamics. ATX-2 forms a complex with SZY-20 in an RNA-independent manner. Depletion of ATX-2 causes embryonic lethality and cytokinesis failure, increases centrosome size and levels of centrosome factors (ZYG-1, SPD-5, γ-Tubulin), and impairs MT growth. ATX-2 influences MT behavior through γ-Tubulin at the centrosome. Co-immunoprecipitation (RNA-independent), RNAi depletion, live imaging, quantitative immunofluorescence in C. elegans embryos PLoS genetics Medium 27689799
2016 C. elegans ATX-2 regulates cytokinesis by targeting ZEN-4 to the spindle midzone through modulation of PAR-5 levels. Preventing ATX-2 function elevates PAR-5 at mitotic structures (spindle, centrosomes, midbody), reducing ZEN-4-GFP at the spindle midzone. Codepletion of ATX-2 and PAR-5 rescues ZEN-4 localization, placing ATX-2 upstream of PAR-5 in this pathway. RNAi depletion, live fluorescence imaging (GFP reporters), genetic epistasis in C. elegans Molecular biology of the cell Medium 27559134
2016 C. elegans atx-2 acts as an mTOR repressor, regulating cell size and fat content under dietary restriction. ATX-2 functions downstream of AMPK and upstream of ribosomal S6 kinase and TORC1 by direct association with Rab GDP dissociation inhibitor β, which likely regulates RHEB shuttling between GDP- and GTP-bound forms. RNAi knockdown, overexpression, genetic pathway analysis, direct interaction assay in C. elegans Proceedings of the National Academy of Sciences of the United States of America Medium 27457958
2000 In SCA2 human brains, ataxin-2 forms cytoplasmic (not nuclear) microaggregates. In transgenic mice expressing ataxin-2[Q58], the protein remains cytoplasmic without detectable ubiquitination, despite causing progressive Purkinje cell dendritic arbor loss and Purkinje cell death. Nuclear localization or inclusion body formation of ataxin-2 are not necessary for SCA2 pathogenesis. Immunohistochemistry of human SCA2 brain tissue, transgenic mouse model with behavioral and neuropathological analysis, subcellular fractionation/immunofluorescence Nature genetics Medium 10973246
2015 FBXW8 (an SCF-type E3 ubiquitin ligase component) co-immunoprecipitates with ATXN2 both in vitro and in vivo, and FBXW8 protein is sequestered into insolubility by expanded ATXN2. PARK2 also co-immunoprecipitates with ATXN2 and FBXW8 and is similarly driven into insolubility by expanded ATXN2. FBXW8 transcript is upregulated by ATXN2 expansion, suggesting FBXW8 mediates degradation of both wildtype and mutant ATXN2. Co-immunoprecipitation in vitro and in vivo, soluble/insoluble fractionation immunoblot, qPCR in patient fibroblasts and blood PloS one Medium 25790475
2019 ATXN2 selectively regulates Nat8l mRNA (encoding the enzyme responsible for N-acetylaspartate synthesis) in an Atxn2-CAG100 knock-in mouse model, with early and strong downregulation of Nat8l transcript before onset of motor deficits. This is associated with reduced N-acetylaspartate brain metabolites detectable by in vivo MR spectroscopy. Knock-in mouse model, RT-qPCR, in vivo MR spectroscopy, transcriptome profiling at pre-symptomatic stages Neurobiology of disease Medium 31376479
2021 In an Atxn2-CAG100 knock-in mouse spinal cord, cytosolic ATXN2 aggregates sequester TDP-43 and TIA1 from the nucleus. This is accompanied by elevated CASP3, RIPK1, and PQBP1 protein levels, and progressive downregulation of cholesterol biosynthesis enzymes (Dhcr24, Msmo1, Idi1, Hmgcs1), with gas chromatography confirming loss of cholesterol precursor metabolites. Knock-in mouse model, triple immunofluorescence, immunoblot, RT-qPCR, transcriptome profiling, gas chromatography Neurobiology of disease Medium 33577922
2017 ATXN2 acts as a strong modifier of PINK1 levels. ATXN2 knockout mouse cerebellum and liver show severe decrease in Pink1 expression alongside effects on Opa1 and Ghitm (mitochondrial dynamics regulators). In human neuroblastoma cells, starvation stress induces ATXN2 and PINK1 in parallel, and knockdown of one enhances expression of the other during stress response. Knockout mouse transcriptome (RNA-seq), RT-qPCR, immunoblot, siRNA knockdown in SH-SY5Y cells, stress induction assay Neurobiology of disease Medium 27597528
2022 ATXN2 augments translation of TNFRSF1A (TNFR1) by binding to m6A-modified TNFRSF1A mRNA, upregulating TNFR1 protein levels and consequently activating NF-κB and MAPK pathways in esophageal squamous cell carcinoma cells. Transcriptome-wide m6A sequencing, RNA immunoprecipitation, functional overexpression/knockdown assays, pathway activation readouts (immunoblot) in ESCC cells Molecular therapy : the journal of the American Society of Gene Therapy Medium 34995801
2015 Repeat-associated non-AUG (RAN) translation occurs for ATXN2 but is weak compared to AUG-dependent translation, does not increase with longer CAG repeat lengths, and is dependent on ATXN2 sequences downstream of the CAG repeat. RAN translation was detected with CMV but not ATXN2 endogenous promoter constructs. Luciferase reporter constructs lacking the ATXN2 AUG start codon, Western blot with anti-polyglutamine antibody, various promoter and truncation constructs in cell culture PloS one Medium 26086378
2017 Atxn2 knockout mouse cerebellum shows dysregulation of calcium homeostasis pathway genes including downregulation of Rora, Itpr1, Atp2a2, and Inpp5a. ITPR1 protein accumulates in membrane-associated fractions in the SCA2 CAG42 knock-in model but not in knockout. Co-immunoprecipitation showed no association of ITPR1 with either Q42-expanded or wild-type ATXN2, indicating the effect on calcium signaling is indirect. Knockout and knock-in mouse models, microarray, RT-qPCR, co-immunoprecipitation, subcellular fractionation immunoblot Cerebellum (London, England) Medium 26868665

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Nuclear localization or inclusion body formation of ataxin-2 are not necessary for SCA2 pathogenesis in mouse or human. Nature genetics 261 10973246
1996 Autosomal dominant cerebellar ataxia type I clinical features and MRI in families with SCA1, SCA2 and SCA3. Brain : a journal of neurology 197 8931575
2008 Spinocerebellar ataxia 2 (SCA2). Cerebellum (London, England) 164 18418684
2006 Ataxin-2 and its Drosophila homolog, ATX2, physically assemble with polyribosomes. Human molecular genetics 162 16835262
2011 Expanded ATXN2 CAG repeat size in ALS identifies genetic overlap between ALS and SCA2. Neurology 147 21562247
2000 Frequency of SCA1, SCA2, SCA3/MJD, SCA6, SCA7, and DRPLA CAG trinucleotide repeat expansion in patients with hereditary spinocerebellar ataxia from Chinese kindreds. Archives of neurology 141 10768629
2010 Rickettsia Sca2 is a bacterial formin-like mediator of actin-based motility. Nature cell biology 136 20972427
2010 Disruption of the Rickettsia rickettsii Sca2 autotransporter inhibits actin-based motility. Infection and immunity 129 20194597
2007 Are interrupted SCA2 CAG repeat expansions responsible for parkinsonism? Neurology 125 17568014
2012 Deranged calcium signaling in Purkinje cells and pathogenesis in spinocerebellar ataxia 2 (SCA2) and other ataxias. Cerebellum (London, England) 120 20480274
1999 Autosomal dominant cerebellar ataxia type I: oculomotor abnormalities in families with SCA1, SCA2, and SCA3. Journal of neurology 119 10525976
2013 A role for Drosophila ATX2 in activation of PER translation and circadian behavior. Science (New York, N.Y.) 114 23687048
2001 CAG repeat instability at SCA2 locus: anchoring CAA interruptions and linked single nucleotide polymorphisms. Human molecular genetics 112 11689490
2005 Generation and characterization of Sca2 (ataxin-2) knockout mice. Biochemical and biophysical research communications 110 16293225
2004 ATX-2, the C. elegans ortholog of ataxin 2, functions in translational regulation in the germline. Development (Cambridge, England) 109 15342467
2002 A Drosophila homolog of the polyglutamine disease gene SCA2 is a dosage-sensitive regulator of actin filament formation. Genetics 104 12524342
1997 Autosomal dominant cerebellar ataxia type I. Nerve conduction and evoked potential studies in families with SCA1, SCA2 and SCA3. Brain : a journal of neurology 104 9448569
2016 ATXN2 trinucleotide repeat length correlates with risk of ALS. Neurobiology of aging 102 28017481
2007 Importance of low-range CAG expansion and CAA interruption in SCA2 Parkinsonism. Archives of neurology 100 17923635
2012 Pathoanatomy of cerebellar degeneration in spinocerebellar ataxia type 2 (SCA2) and type 3 (SCA3). Cerebellum (London, England) 88 22198871
1998 The role of the SCA2 trinucleotide repeat expansion in 89 autosomal dominant cerebellar ataxia families. Frequency, clinical and genetic correlates. Brain : a journal of neurology 86 9549522
2011 PolyQ repeat expansions in ATXN2 associated with ALS are CAA interrupted repeats. PloS one 84 21479228
2012 ATXN2-CAG42 sequesters PABPC1 into insolubility and induces FBXW8 in cerebellum of old ataxic knock-in mice. PLoS genetics 76 22956915
2009 The Sca2 autotransporter protein from Rickettsia conorii is sufficient to mediate adherence to and invasion of cultured mammalian cells. Infection and immunity 76 19805531
1988 The stem cell antigens Sca-1 and Sca-2 subdivide thymic and peripheral T lymphocytes into unique subsets. Journal of immunology (Baltimore, Md. : 1950) 76 2460547
2016 Ataxin-2 (Atxn2)-Knock-Out Mice Show Branched Chain Amino Acids and Fatty Acids Pathway Alterations. Molecular & cellular proteomics : MCP 74 26850065
2011 Association of long ATXN2 CAG repeat sizes with increased risk of amyotrophic lateral sclerosis. Archives of neurology 74 21670397
2015 Ataxin-2 regulates RGS8 translation in a new BAC-SCA2 transgenic mouse model. PLoS genetics 72 25902068
1997 SCA2 trinucleotide expansion in German SCA patients. Neurogenetics 70 10735276
2003 SCA2 may present as levodopa-responsive parkinsonism. Movement disorders : official journal of the Movement Disorder Society 68 12671950
2014 Contribution of ATXN2 intermediary polyQ expansions in a spectrum of neurodegenerative disorders. Neurology 67 25098532
1996 Suppression of oxidative damage by Saccharomyces cerevisiae ATX2, which encodes a manganese-trafficking protein that localizes to Golgi-like vesicles. Molecular and cellular biology 67 8887660
2016 Cell size and fat content of dietary-restricted Caenorhabditis elegans are regulated by ATX-2, an mTOR repressor. Proceedings of the National Academy of Sciences of the United States of America 62 27457958
1998 A clinicogenetic analysis of six Indian spinocerebellar ataxia (SCA2) pedigrees. The significance of slow saccades in diagnosis. Brain : a journal of neurology 62 9874485
2014 Amyotrophic lateral sclerosis risk for spinocerebellar ataxia type 2 ATXN2 CAG repeat alleles: a meta-analysis. JAMA neurology 61 25285812
2006 Stages of sleep pathology in spinocerebellar ataxia type 2 (SCA2). Neurology 59 17159102
2004 Patterns of CAG repeat interruptions in SCA1 and SCA2 genes in relation to repeat instability. Human mutation 58 15300851
2016 In vivo analysis of cerebellar Purkinje cell activity in SCA2 transgenic mouse model. Journal of neurophysiology 57 26984424
2016 ATXN2-AS, a gene antisense to ATXN2, is associated with spinocerebellar ataxia type 2 and amyotrophic lateral sclerosis. Annals of neurology 57 27531668
2015 No parkinsonism in SCA2 and SCA3 despite severe neurodegeneration of the dopaminergic substantia nigra. Brain : a journal of neurology 57 26362908
2002 Childhood-onset ataxia: testing for large CAG-repeats in SCA2 and SCA7. American journal of medical genetics 57 12116207
2011 ATXN-2 CAG repeat expansions are interrupted in ALS patients. Human genetics 54 21537950
2017 Atxn2 Knockout and CAG42-Knock-in Cerebellum Shows Similarly Dysregulated Expression in Calcium Homeostasis Pathway. Cerebellum (London, England) 53 26868665
1998 Analysis of SCA1, DRPLA, MJD, SCA2, and SCA6 CAG repeats in 48 Portuguese ataxia families. American journal of medical genetics 53 9613852
2017 Evidence of oxidative stress and mitochondrial dysfunction in spinocerebellar ataxia type 2 (SCA2) patient fibroblasts: Effect of coenzyme Q10 supplementation on these parameters. Mitochondrion 52 28263872
2014 12q24 locus association with type 1 diabetes: SH2B3 or ATXN2? World journal of diabetes 52 24936253
2014 ATXN2 polyQ intermediate repeats are a modifier of ALS survival. Neurology 52 25527265
2004 Autosomal dominant cerebellar ataxia: SCA2 is the most frequent mutation in eastern India. Journal of neurology, neurosurgery, and psychiatry 49 14966163
2003 Identification of chicken lymphocyte antigen 6 complex, locus E (LY6E, alias SCA2) as a putative Marek's disease resistance gene via a virus-host protein interaction screen. Cytogenetic and genome research 49 14970721
1995 Modulation of TCR-mediated signaling pathway by thymic shared antigen-1 (TSA-1)/stem cell antigen-2 (Sca-2). Journal of immunology (Baltimore, Md. : 1950) 48 7499840
2013 Rickettsia Sca2 has evolved formin-like activity through a different molecular mechanism. Proceedings of the National Academy of Sciences of the United States of America 46 23818602
1999 Clinical and molecular studies of 73 Italian families with autosomal dominant cerebellar ataxia type I: SCA1 and SCA2 are the most common genotypes. Journal of neurology 44 10399872
2021 Atxn2-CAG100-KnockIn mouse spinal cord shows progressive TDP43 pathology associated with cholesterol biosynthesis suppression. Neurobiology of disease 43 33577922
1996 Autosomal dominant cerebellar ataxia type I: multimodal electrophysiological study and comparison between SCA1 and SCA2 patients. Journal of the neurological sciences 43 8902719
2011 Massive expansion of SCA2 with autonomic dysfunction, retinitis pigmentosa, and infantile spasms. Neurology 42 21880993
2011 Unexpanded and intermediate CAG polymorphisms at the SCA2 locus (ATXN2) in the Cuban population: evidence about the origin of expanded SCA2 alleles. European journal of human genetics : EJHG 42 21934711
2008 Intrafamilial variability of Parkinson phenotype in SCAs: novel cases due to SCA2 and SCA3 expansions. Parkinsonism & related disorders 42 18990604
2005 Positive selection of a pre-expansion CAG repeat of the human SCA2 gene. PLoS genetics 41 16205789
2014 Intermediate CAG repeat expansion in the ATXN2 gene is a unique genetic risk factor for ALS--a systematic review and meta-analysis of observational studies. PloS one 40 25148523
2012 ATXN2 and its neighbouring gene SH2B3 are associated with increased ALS risk in the Turkish population. PloS one 39 22916186
2016 The most prevalent genetic cause of ALS-FTD, C9orf72 synergizes the toxicity of ATXN2 intermediate polyglutamine repeats through the autophagy pathway. Autophagy 38 27245636
2009 Analysis of SCA2 and SCA3/MJD repeats in Parkinson's disease in mainland China: genetic, clinical, and positron emission tomography findings. Movement disorders : official journal of the Movement Disorder Society 38 19672991
2022 ATXN2 intermediate expansions in amyotrophic lateral sclerosis. Brain : a journal of neurology 37 35521889
2019 Role for ATXN1, ATXN2, and HTT intermediate repeats in frontotemporal dementia and Alzheimer's disease. Neurobiology of aging 37 31810584
2004 Abnormalities of dopaminergic neurotransmission in SCA2: a combined 123I-betaCIT and 123I-IBZM SPECT study. Movement disorders : official journal of the Movement Disorder Society 36 15390003
2004 Caenorhabditis elegans atx-2 promotes germline proliferation and the oocyte fate. Genetics 36 15514056
2005 Ubiquitous expression of human SCA2 gene under the regulation of the SCA2 self promoter cause specific Purkinje cell degeneration in transgenic mice. Neuroscience letters 34 16203087
2004 Spinocerebellar ataxia type 2 (SCA2) presenting with ophthalmoplegia and developmental delay in infancy. American journal of medical genetics. Part A 34 14735588
2016 Cerebellar neuronal loss in amyotrophic lateral sclerosis cases with ATXN2 intermediate repeat expansions. Annals of neurology 33 26599997
2015 Repeat Associated Non-AUG Translation (RAN Translation) Dependent on Sequence Downstream of the ATXN2 CAG Repeat. PloS one 33 26086378
2013 ATXN2 CAG repeat expansions increase the risk for Chinese patients with amyotrophic lateral sclerosis. Neurobiology of aging 33 23635656
2010 The KRAB-containing zinc-finger transcriptional regulator ZBRK1 activates SCA2 gene transcription through direct interaction with its gene product, ataxin-2. Human molecular genetics 33 20926453
1996 Autosomal dominant cerebellar ataxia type I. Clinical and molecular study in 36 Italian families including a comparison between SCA1 and SCA2 phenotypes. Journal of the neurological sciences 33 8902734
2019 Generation of an Atxn2-CAG100 knock-in mouse reveals N-acetylaspartate production deficit due to early Nat8l dysregulation. Neurobiology of disease 31 31376479
2017 Early corticospinal tract damage in prodromal SCA2 revealed by EEG-EMG and EMG-EMG coherence. Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology 31 29101844
1997 Frequency of the different mutations causing spinocerebellar ataxia (SCA1, SCA2, MJD/SCA3 and DRPLA) in a large group of Brazilian patients. Arquivos de neuro-psiquiatria 31 9629399
2016 Search for SCA2 blood RNA biomarkers highlights Ataxin-2 as strong modifier of the mitochondrial factor PINK1 levels. Neurobiology of disease 30 27597528
2016 ATX-2, the C. elegans Ortholog of Human Ataxin-2, Regulates Centrosome Size and Microtubule Dynamics. PLoS genetics 30 27689799
2012 ETS1 regulates the expression of ATXN2. Human molecular genetics 30 22914732
2024 The polyglutamine protein ATXN2: from its molecular functions to its involvement in disease. Cell death & disease 29 38877004
2021 SCA7 Mouse Cerebellar Pathology Reveals Preferential Downregulation of Key Purkinje Cell-Identity Genes and Shared Disease Signature with SCA1 and SCA2. The Journal of neuroscience : the official journal of the Society for Neuroscience 29 33888607
2016 Abnormal corticospinal tract function and motor cortex excitability in non-ataxic SCA2 mutation carriers: A TMS study. Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology 29 27417041
2022 ATXN2-mediated translation of TNFR1 promotes esophageal squamous cell carcinoma via m6A-dependent manner. Molecular therapy : the journal of the American Society of Gene Therapy 28 34995801
2011 Spinocerebellar ataxia type 2 (SCA2): identification of early brain degeneration in one monozygous twin in the initial disease stage. Cerebellum (London, England) 28 21128038
2020 ALS-associated genes in SCA2 mouse spinal cord transcriptomes. Human molecular genetics 27 32307524
2018 Role of Sca2 and RickA in the Dissemination of Rickettsia parkeri in Amblyomma maculatum. Infection and immunity 27 29581194
2014 FTLD-ALS of TDP-43 type and SCA2 in a family with a full ataxin-2 polyglutamine expansion. Acta neuropathologica 27 24718895
2010 Common origin of pure and interrupted repeat expansions in spinocerebellar ataxia type 2 (SCA2). American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 27 19676102
2018 ATXN2 intermediate repeat expansions influence the clinical phenotype in frontotemporal dementia. Neurobiology of aging 26 30342763
2003 Searching for modulating effects of SCA2, SCA6 and DRPLA CAG tracts on the Machado-Joseph disease (SCA3) phenotype. Acta neurologica Scandinavica 26 12614315
2021 LINC00941 promotes proliferation and metastasis of pancreatic adenocarcinoma by competitively binding miR-873-3p and thus upregulates ATXN2. European review for medical and pharmacological sciences 25 33660796
2015 Both ubiquitin ligases FBXW8 and PARK2 are sequestrated into insolubility by ATXN2 PolyQ expansions, but only FBXW8 expression is dysregulated. PloS one 25 25790475
2015 ATXN2 is a modifier of phenotype in ALS patients of Sardinian ancestry. Neurobiology of aging 25 26208502
2001 Molecular analysis of Spinocerebellar ataxias in Koreans: frequencies and reference ranges of SCA1, SCA2, SCA3, SCA6, and SCA7. Molecules and cells 25 11804332
2019 TDP-43 levels in the brain tissue of ALS cases with and without C9ORF72 or ATXN2 gene expansions. Neurology 23 31619481
2016 The RNA-binding protein ATX-2 regulates cytokinesis through PAR-5 and ZEN-4. Molecular biology of the cell 21 27559134
2012 Identification and characterization of the mammalian association and actin-nucleating domains in the Rickettsia conorii autotransporter protein, Sca2. Cellular microbiology 21 22612237
1996 Central phenotype and related varieties of spinocerebellar ataxia 2 (SCA2): a clinical and genetic study with a pedigree in the Japanese. Journal of the neurological sciences 20 8994121
2017 SCA2 family presenting as typical Parkinson's disease: 34 year follow up. Parkinsonism & related disorders 18 28462804
2022 ATXN2-Mediated PI3K/AKT Activation Confers Gastric Cancer Chemoresistance and Attenuates CD8+ T Cell Cytotoxicity. Journal of immunology research 17 36213324

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